DESCRIPTION: (Investigator's Abstract); The long term goal of this proposal is to improve the efficiency of conventional tumor therapy by pharmacological approaches utilizing high doses of multiple antioxidant vitamins. Although the effects of individual vitamins" such as retinoids, beta-carotene, vitamin E, vitamin C and vitamin D on the growth and differentiation of certain tumor cells in vitro have been investigated, the effects of a mixture of high doses of these vitamins in combination with conventional tumor therapeutic agents on human tumor cells has not yet been investigated in a systematic manner. This is an essential first step before using them in clinical trials. The specific aim of this proposal is to investigate the effects of individual and a mixture of high doses of antioxidant vitamins in combination with radiation and chemotherapeutic agents on the survival and growth of human melanoma and squamous cell carcinoma in culture.Our working hypothesis is that high doses of vitamin mixture may enhance the growth inhibitory effect of tumor therapeutic agents on tumor cells, but they may protect normal cells against the adverse effects of therapeutic agents. The proposed study will test the first part of this hypothesis. If the dose-response curves show that high doses of vitamins alone or in a mixture enhance the growth inhibitory effects of therapeutic agents on human tumor cells in vitro, a protocol which will involve two treatment arms, one with conventional therapy and the other with conventional therapy plus high doses of a mixture of vitamins will be developed for the treatment of melanoma and squamous cell carcinoma.An oncologist is a co-investigator on this project, and a radiation therapist has agreed to initiate clinical trials if laboratory data appear encouraging. (The letters of agreement are attached to this application).